4usm: Difference between revisions

Line 1:

'''~~Unreleased~~ structure'''

==WcbL complex with glycerol bound to sugar site==

== Structural highlights ==

<table><tr><td colspan='2'>[[4usm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4USM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4USM FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4usk|4usk]]</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/D-glycero-beta-D-manno-heptose-7-phosphate_kinase D-glycero-beta-D-manno-heptose-7-phosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.167 2.7.1.167] </span></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4usm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4usm OCA], [http://pdbe.org/4usm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4usm RCSB], [http://www.ebi.ac.uk/pdbsum/4usm PDBsum]</span></td></tr>

</table>

== Publication Abstract from PubMed ==

Gram-negative bacteria utilize heptoses as part of their repertoire of extracellular polysaccharide virulence determinants. Disruption of heptose biosynthesis offers an attractive target for novel antimicrobials. A critical step in the synthesis of heptoses is their 1-O phosphorylation, mediated by kinases such as HldE or WcbL. Here, we present the structure of WcbL from Burkholderia pseudomallei. We report that WcbL operates through a sequential ordered Bi-Bi mechanism, loading the heptose first and then ATP. We show that dimeric WcbL binds ATP anti-cooperatively in the absence of heptose, and cooperatively in its presence. Modeling of WcbL suggests that heptose binding causes an elegant switch in the hydrogen-bonding network, facilitating the binding of a second ATP molecule. Finally, we screened a library of drug-like fragments, identifying hits that potently inhibit WcbL. Our results provide a novel mechanism for control of substrate binding and emphasize WcbL as an attractive anti-microbial target for Gram-negative bacteria.

~~The entry 4usm is ON HOLD until Paper Publication~~

Unraveling the B. pseudomallei Heptokinase WcbL: From Structure to Drug Discovery.,Vivoli M, Isupov MN, Nicholas R, Hill A, Scott AE, Kosma P, Prior JL, Harmer NJ Chem Biol. 2015 Dec 17;22(12):1622-32. doi: 10.1016/j.chembiol.2015.10.015. PMID:26687481<ref>PMID:26687481</ref>

~~Authors: Vivoli~~, M.~~, Isupov, M~~.~~N., Nicholas, R., Hill, A., Scott, A., Kosma, P., Prior, J., Harmer, N.J~~.

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

</div>

~~Description~~: ~~WcbL complex with glycerol bound to sugar site~~

[[Category: ~~Unreleased Structures~~]]

== References ==

[[Category: ~~Prior~~, J]]

~~[[Category: Vivoli, M~~]]

__TOC__

</StructureSection>

[[Category: D-glycero-beta-D-manno-heptose-7-phosphate kinase]]

[[Category: Harmer, N J]]

[[Category: Hill, A]]

[[Category: Isupov, M N]]

[[Category: Kosma, P]]

[[Category: Nicholas, R]]

[[Category: ~~Isupov~~, ~~M.N]]~~

[[Category: Prior, J]]

~~[[Category: Kosma, P~~]]

[[Category: Scott, A]]

[[Category: ~~Harmer~~, ~~N.J~~]]

[[Category: Vivoli, M]]

[[Category: Capsular polysaccharide]]

[[Category: Drug discovery]]

[[Category: Heptopyranose]]

[[Category: Transferase]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
+==WcbL complex with glycerol bound to sugar site==
+<StructureSection load='4usm' size='340' side='right' caption='[[4usm]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[4usm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4USM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4USM FirstGlance]. <br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4usk|4usk]]</td></tr>
+<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/D-glycero-beta-D-manno-heptose-7-phosphate_kinase D-glycero-beta-D-manno-heptose-7-phosphate kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.1.167 2.7.1.167] </span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4usm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4usm OCA], [http://pdbe.org/4usm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4usm RCSB], [http://www.ebi.ac.uk/pdbsum/4usm PDBsum]</span></td></tr>
+</table>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Gram-negative bacteria utilize heptoses as part of their repertoire of extracellular polysaccharide virulence determinants. Disruption of heptose biosynthesis offers an attractive target for novel antimicrobials. A critical step in the synthesis of heptoses is their 1-O phosphorylation, mediated by kinases such as HldE or WcbL. Here, we present the structure of WcbL from Burkholderia pseudomallei. We report that WcbL operates through a sequential ordered Bi-Bi mechanism, loading the heptose first and then ATP. We show that dimeric WcbL binds ATP anti-cooperatively in the absence of heptose, and cooperatively in its presence. Modeling of WcbL suggests that heptose binding causes an elegant switch in the hydrogen-bonding network, facilitating the binding of a second ATP molecule. Finally, we screened a library of drug-like fragments, identifying hits that potently inhibit WcbL. Our results provide a novel mechanism for control of substrate binding and emphasize WcbL as an attractive anti-microbial target for Gram-negative bacteria.
-The entry 4usm is ON HOLD  until Paper Publication
+Unraveling the B. pseudomallei Heptokinase WcbL: From Structure to Drug Discovery.,Vivoli M, Isupov MN, Nicholas R, Hill A, Scott AE, Kosma P, Prior JL, Harmer NJ Chem Biol. 2015 Dec 17;22(12):1622-32. doi: 10.1016/j.chembiol.2015.10.015. PMID:26687481<ref>PMID:26687481</ref>
-Authors: Vivoli, M., Isupov, M.N., Nicholas, R., Hill, A., Scott, A., Kosma, P., Prior, J., Harmer, N.J.
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
+</div>
-Description: WcbL complex with glycerol bound to sugar site
+<div class="pdbe-citations 4usm" style="background-color:#fffaf0;"></div>
-[[Category: Unreleased Structures]]
+== References ==
-[[Category: Prior, J]]
+<references/>
-[[Category: Vivoli, M]]
+__TOC__
+</StructureSection>
+[[Category: D-glycero-beta-D-manno-heptose-7-phosphate kinase]]
+[[Category: Harmer, N J]]
 [[Category: Hill, A]]
+[[Category: Isupov, M N]]
+[[Category: Kosma, P]]
 [[Category: Nicholas, R]]
-[[Category: Isupov, M.N]]
+[[Category: Prior, J]]
-[[Category: Kosma, P]]
 [[Category: Scott, A]]
-[[Category: Harmer, N.J]]
+[[Category: Vivoli, M]]
+[[Category: Capsular polysaccharide]]
+[[Category: Drug discovery]]
+[[Category: Heptopyranose]]
+[[Category: Transferase]]